KR102638678B1 - 헤테로시클릭 화합물 - Google Patents
헤테로시클릭 화합물 Download PDFInfo
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- KR102638678B1 KR102638678B1 KR1020197031604A KR20197031604A KR102638678B1 KR 102638678 B1 KR102638678 B1 KR 102638678B1 KR 1020197031604 A KR1020197031604 A KR 1020197031604A KR 20197031604 A KR20197031604 A KR 20197031604A KR 102638678 B1 KR102638678 B1 KR 102638678B1
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- South Korea
- Prior art keywords
- group
- alkyl
- substituted
- membered
- substituents selected
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- 150000002391 heterocyclic compounds Chemical class 0.000 title description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 85
- 150000001875 compounds Chemical class 0.000 claims abstract description 47
- 208000019622 heart disease Diseases 0.000 claims abstract description 18
- 206010019280 Heart failures Diseases 0.000 claims abstract description 15
- 206010003119 arrhythmia Diseases 0.000 claims abstract description 12
- 230000006793 arrhythmia Effects 0.000 claims abstract description 11
- 201000000015 catecholaminergic polymorphic ventricular tachycardia Diseases 0.000 claims abstract description 10
- 206010003658 Atrial Fibrillation Diseases 0.000 claims abstract description 9
- 230000002980 postoperative effect Effects 0.000 claims abstract description 9
- -1 mono-substituted amino group Chemical group 0.000 claims description 659
- 125000001424 substituent group Chemical group 0.000 claims description 658
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 588
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 455
- 125000005843 halogen group Chemical group 0.000 claims description 396
- 125000002950 monocyclic group Chemical group 0.000 claims description 317
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 257
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 235
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 223
- 125000003118 aryl group Chemical group 0.000 claims description 177
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 153
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 136
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 134
- 125000005936 piperidyl group Chemical group 0.000 claims description 110
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 87
- 125000003277 amino group Chemical group 0.000 claims description 80
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 79
- 125000004043 oxo group Chemical group O=* 0.000 claims description 78
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 67
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 65
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 63
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 59
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 54
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 51
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 49
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 44
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 44
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 43
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 39
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 35
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 31
- 125000002883 imidazolyl group Chemical group 0.000 claims description 27
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 20
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 20
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 20
- 125000005974 C6-C14 arylcarbonyl group Chemical group 0.000 claims description 18
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 15
- 229910052805 deuterium Inorganic materials 0.000 claims description 14
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 14
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 125000003003 spiro group Chemical group 0.000 claims description 6
- 101710116137 Calcium/calmodulin-dependent protein kinase II Proteins 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 3
- GUEJTWUSAZVRKO-FQEVSTJZSA-N 1-[4-[[5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]pyrimidin-2-yl]amino]-1-[2-(oxan-4-yl)-2-azaspiro[3.3]heptan-6-yl]pyrazol-3-yl]propan-1-one Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)C2CCOCC2)C1)C(CC)=O GUEJTWUSAZVRKO-FQEVSTJZSA-N 0.000 claims description 2
- VPONJUYFECMEFR-SFHVURJKSA-N 1-[6-[4-[[5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]pyrimidin-2-yl]amino]-3-(2,2,2-trifluoroethoxy)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-2-methylpropan-2-ol Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)CC(C)(O)C)C1)OCC(F)(F)F VPONJUYFECMEFR-SFHVURJKSA-N 0.000 claims description 2
- MNIXFPJTOHARAF-KRWDZBQOSA-N 1-[6-[4-[[5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]pyrimidin-2-yl]amino]-3-(trifluoromethyl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-2-methylpropan-2-ol Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)CC(C)(O)C)C1)C(F)(F)F MNIXFPJTOHARAF-KRWDZBQOSA-N 0.000 claims description 2
- PVOMAXPFRUBALC-FQEVSTJZSA-N 1-[6-[4-[[5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]pyrimidin-2-yl]amino]-3-propan-2-ylpyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]-2-methylpropan-2-ol Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)CC(C)(O)C)C1)C(C)C PVOMAXPFRUBALC-FQEVSTJZSA-N 0.000 claims description 2
- WJGDMVPILKZMAV-FQEVSTJZSA-N 4-[2-[[1-[1-(oxan-4-yl)piperidin-4-yl]-3-(2,2,2-trifluoroethoxy)pyrazol-4-yl]amino]pyrimidin-5-yl]-2-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxybenzonitrile Chemical compound N1(N=NN=C1)C[C@H](C)OC1=C(C#N)C=CC(=C1)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CCN(CC1)C1CCOCC1)OCC(F)(F)F WJGDMVPILKZMAV-FQEVSTJZSA-N 0.000 claims description 2
- VQCKTHAMBHIOAB-IBGZPJMESA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[1-(oxan-4-yl)piperidin-4-yl]-3-(2,2,2-trifluoroethoxy)pyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CCN(CC1)C1CCOCC1)OCC(F)(F)F VQCKTHAMBHIOAB-IBGZPJMESA-N 0.000 claims description 2
- KRPFBRADNLJEHU-SFHVURJKSA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[1-(oxan-4-yl)piperidin-4-yl]-3-(trifluoromethyl)pyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CCN(CC1)C1CCOCC1)C(F)(F)F KRPFBRADNLJEHU-SFHVURJKSA-N 0.000 claims description 2
- HHXMCUQFSJVOON-NRFANRHFSA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[1-(oxan-4-yl)piperidin-4-yl]-3-propan-2-ylpyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CCN(CC1)C1CCOCC1)C(C)C HHXMCUQFSJVOON-NRFANRHFSA-N 0.000 claims description 2
- WWZYYXAGNVCVAV-IBGZPJMESA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[2-(2,2-dimethyl-1,3-dioxan-5-yl)-2-azaspiro[3.3]heptan-6-yl]-3-(2,2,2-trifluoroethoxy)pyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)C2COC(OC2)(C)C)C1)OCC(F)(F)F WWZYYXAGNVCVAV-IBGZPJMESA-N 0.000 claims description 2
- WUIRPMRRXBWOHY-FQEVSTJZSA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[2-(4-methyloxan-4-yl)-2-azaspiro[3.3]heptan-6-yl]-3-(2,2,2-trifluoroethoxy)pyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)C2(CCOCC2)C)C1)OCC(F)(F)F WUIRPMRRXBWOHY-FQEVSTJZSA-N 0.000 claims description 2
- JYIBKGVPNNTKDX-QFIPXVFZSA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[2-(4-methyloxan-4-yl)-2-azaspiro[3.3]heptan-6-yl]-3-propan-2-ylpyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)C2(CCOCC2)C)C1)C(C)C JYIBKGVPNNTKDX-QFIPXVFZSA-N 0.000 claims description 2
- LMSMDIADEKRPSY-SFHVURJKSA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[2-(oxan-4-yl)-2-azaspiro[3.3]heptan-6-yl]-3-(1,1,2,2,2-pentafluoroethyl)pyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)C2CCOCC2)C1)C(C(F)(F)F)(F)F LMSMDIADEKRPSY-SFHVURJKSA-N 0.000 claims description 2
- OUHZZBHSIRSLDC-IBGZPJMESA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[2-(oxan-4-yl)-2-azaspiro[3.3]heptan-6-yl]-3-(2,2,2-trifluoroethoxy)pyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)C2CCOCC2)C1)OCC(F)(F)F OUHZZBHSIRSLDC-IBGZPJMESA-N 0.000 claims description 2
- RQRQJHHWHWDXNM-SFHVURJKSA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[2-(oxan-4-yl)-2-azaspiro[3.3]heptan-6-yl]-3-(trifluoromethyl)pyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)C2CCOCC2)C1)C(F)(F)F RQRQJHHWHWDXNM-SFHVURJKSA-N 0.000 claims description 2
- DMNAGTPREZOPLB-NRFANRHFSA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[2-(oxan-4-yl)-2-azaspiro[3.3]heptan-6-yl]-3-propan-2-ylpyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)C2CCOCC2)C1)C(C)C DMNAGTPREZOPLB-NRFANRHFSA-N 0.000 claims description 2
- ADNKOHLRCDLGKN-KRWDZBQOSA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[2-(oxetan-3-yl)-2-azaspiro[3.3]heptan-6-yl]-3-(2,2,2-trifluoroethoxy)pyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)C2COC2)C1)OCC(F)(F)F ADNKOHLRCDLGKN-KRWDZBQOSA-N 0.000 claims description 2
- NLBBLRXCADWLBC-IBGZPJMESA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[1-[2-(oxetan-3-yl)-2-azaspiro[3.3]heptan-6-yl]-3-propan-2-ylpyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CC2(CN(C2)C2COC2)C1)C(C)C NLBBLRXCADWLBC-IBGZPJMESA-N 0.000 claims description 2
- OWRBXYCSJVJQJG-SFHVURJKSA-N 5-[4-chloro-3-[(2S)-1-(tetrazol-1-yl)propan-2-yl]oxyphenyl]-N-[3-(difluoromethoxy)-1-[1-(oxan-4-yl)piperidin-4-yl]pyrazol-4-yl]pyrimidin-2-amine Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)C1CCN(CC1)C1CCOCC1)OC(F)F OWRBXYCSJVJQJG-SFHVURJKSA-N 0.000 claims description 2
- NPVRVFOIFBKRSE-OPXMRZJTSA-N N1(N=NN=C1)C[C@H](C)OC1=C(C#N)C=CC(=C1)C=1C=NC(=NC=1)NC=1C(=NN(C=1)[C@@H]1CC[C@H](CC1)N1CCOCC1)OCC(F)(F)F Chemical compound N1(N=NN=C1)C[C@H](C)OC1=C(C#N)C=CC(=C1)C=1C=NC(=NC=1)NC=1C(=NN(C=1)[C@@H]1CC[C@H](CC1)N1CCOCC1)OCC(F)(F)F NPVRVFOIFBKRSE-OPXMRZJTSA-N 0.000 claims description 2
- MADBBKDUWITXRE-NYVOZVTQSA-N N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)[C@@H]1CC[C@H](CC1)N1CC(C1)(O)C)OCC(F)(F)F Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)[C@@H]1CC[C@H](CC1)N1CC(C1)(O)C)OCC(F)(F)F MADBBKDUWITXRE-NYVOZVTQSA-N 0.000 claims description 2
- LIWJUHROADWDGD-TUSQITKMSA-N N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)[C@@H]1CC[C@H](CC1)N1CCOCC1)C(C)C Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)[C@@H]1CC[C@H](CC1)N1CCOCC1)C(C)C LIWJUHROADWDGD-TUSQITKMSA-N 0.000 claims description 2
- MJHNRVFASZBKFR-VDVKDMFPSA-N N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)[C@@H]1CC[C@H](CC1)N1CCOCC1)OC[C@H]1C(C1)(F)F Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)[C@@H]1CC[C@H](CC1)N1CCOCC1)OC[C@H]1C(C1)(F)F MJHNRVFASZBKFR-VDVKDMFPSA-N 0.000 claims description 2
- UOCOSTUNIVSDPU-FUBBUTDDSA-N N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)[C@@H]1CC[C@H](CC1)N1[C@H]2COC[C@@H]1CC2)OCC(F)F Chemical compound N1(N=NN=C1)C[C@H](C)OC=1C=C(C=CC=1Cl)C=1C=NC(=NC=1)NC=1C(=NN(C=1)[C@@H]1CC[C@H](CC1)N1[C@H]2COC[C@@H]1CC2)OCC(F)F UOCOSTUNIVSDPU-FUBBUTDDSA-N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000004431 deuterium atom Chemical group 0.000 claims 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 2
- UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical group C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 claims 1
- 102000004657 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Human genes 0.000 abstract description 21
- 108010003721 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proteins 0.000 abstract description 21
- 238000011282 treatment Methods 0.000 abstract description 14
- 230000002401 inhibitory effect Effects 0.000 abstract description 8
- 230000002265 prevention Effects 0.000 abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 217
- 125000001153 fluoro group Chemical group F* 0.000 description 201
- 229910052731 fluorine Inorganic materials 0.000 description 170
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 111
- 229910052799 carbon Inorganic materials 0.000 description 109
- 150000001721 carbon Chemical group 0.000 description 108
- 125000002757 morpholinyl group Chemical group 0.000 description 101
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 80
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 78
- 125000003566 oxetanyl group Chemical group 0.000 description 78
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 69
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 64
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 61
- 125000004433 nitrogen atom Chemical group N* 0.000 description 53
- 229910052757 nitrogen Inorganic materials 0.000 description 48
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 46
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 42
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 41
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 41
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 40
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 34
- 125000001309 chloro group Chemical group Cl* 0.000 description 33
- 229910052801 chlorine Inorganic materials 0.000 description 31
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 31
- 125000004193 piperazinyl group Chemical group 0.000 description 30
- 125000002393 azetidinyl group Chemical group 0.000 description 27
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 27
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 26
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- 125000006337 tetrafluoro ethyl group Chemical group 0.000 description 1
- ZXLDQJLIBNPEFJ-UHFFFAOYSA-N tetrahydro-beta-carboline Natural products C1CNC(C)C2=C1C1=CC=C(OC)C=C1N2 ZXLDQJLIBNPEFJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
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| US201762476970P | 2017-03-27 | 2017-03-27 | |
| US62/476,970 | 2017-03-27 | ||
| PCT/US2018/024043 WO2018183112A1 (en) | 2017-03-27 | 2018-03-23 | Heterocyclic compound |
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| KR20200027917A KR20200027917A (ko) | 2020-03-13 |
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| TW (1) | TWI789381B (ru) |
| WO (1) | WO2018183112A1 (ru) |
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| AU2018243691B2 (en) | 2017-03-27 | 2022-05-12 | Cardurion Pharmaceuticals, Llc | Heterocyclic compound |
| RU2020124138A (ru) | 2017-12-22 | 2022-01-24 | Хиберселл, Инк. | Производные аминопиридина в качестве ингибиторов фосфатидилинозитолфосфаткиназы |
| WO2020068846A1 (en) * | 2018-09-25 | 2020-04-02 | Heterocyclic Compound | Heterocyclic compound |
| KR20210082454A (ko) * | 2018-09-25 | 2021-07-05 | 카듀리온 파마슈티칼스, 인크. | 아미노피리미딘 화합물 |
| TW202112767A (zh) | 2019-06-17 | 2021-04-01 | 美商佩特拉製藥公司 | 作為磷脂酸肌醇磷酸激酶抑制劑之胺基吡啶衍生物 |
| JP2022552735A (ja) * | 2019-10-25 | 2022-12-19 | ギリアード サイエンシーズ， インコーポレイテッド | Ｇｌｐ－１ｒ調節化合物 |
| EP4119555A4 (en) * | 2020-03-18 | 2023-08-23 | Lg Chem, Ltd. | GLP-1 RECEPTOR AGONIST, PHARMACEUTICAL COMPOSITION THEREOF AND PROCESS FOR MANUFACTURE THEREOF |
| AU2021237185B2 (en) * | 2020-03-18 | 2023-11-30 | Lg Chem, Ltd. | GLP-1 receptor agonist, pharmaceutical composition comprising same, and method for preparing same |
| CA3196946A1 (en) | 2020-09-28 | 2022-03-31 | Cardurion Pharmaceuticals, Inc. | Fused heteroaryl compounds and their use as camkii inhibitors |
| WO2022109182A1 (en) | 2020-11-20 | 2022-05-27 | Gilead Sciences, Inc. | Polyheterocyclic glp-1 r modulating compounds |
| WO2022216094A1 (ko) * | 2021-04-08 | 2022-10-13 | 주식회사 엘지화학 | Glp-1 수용체 효능제, 이를 포함하는 약학적 조성물 및 이의 제조방법 |
| KR20230173708A (ko) | 2021-04-21 | 2023-12-27 | 길리애드 사이언시즈, 인코포레이티드 | 카르복시-벤즈이미다졸 glp-1r 조절 화합물 |
| WO2023130050A1 (en) * | 2021-12-29 | 2023-07-06 | Psy Therapeutics, Inc. | Monoacylglycerol lipase inhibitors and use thereof for the treatment and management of pain |
| CN114621312B (zh) * | 2022-03-24 | 2022-11-15 | 陕西师范大学 | 一种寡肽烷基侧链的选择性修饰方法 |
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| WO2002011724A2 (en) | 2000-08-08 | 2002-02-14 | Ortho-Mcneil Pharmaceutical, Inc. | Neuroprotective 2-pyridinamine compositions and related methods |
| WO2010057833A1 (en) | 2008-11-21 | 2010-05-27 | Biomarin Iga, Ltd. | Compounds for treatment of duchenne muscular dystrophy |
| JP2010523568A (ja) * | 2007-04-05 | 2010-07-15 | アムジエン・インコーポレーテツド | オーロラキナーゼ調節物質及び使用方法 |
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| CA2423050A1 (en) | 2000-09-20 | 2002-03-28 | Ortho-Mcneil Pharmaceutical, Inc. | Pyrazine derivatives as modulators of tyrosine kinases |
| BRPI0412347A (pt) | 2003-07-30 | 2006-09-05 | Cyclacel Ltd | 2-aminofenil-4-fenilpiridinas como inibidores de quinase |
| AU2004268112A1 (en) | 2003-09-02 | 2005-03-10 | Merck & Co., Inc. | Bipyridyl amines and ethers as modulators of metabotropic glutamate receptor-5 |
| AU2008296479A1 (en) * | 2007-08-28 | 2009-03-12 | Dana Farber Cancer Institute | Amino substituted pyrimidine, pyrollopyridine and pyrazolopyrimidine derivatives useful as kinase inhibitors and in treating proliferative disorders and diseases associated with angiogenesis |
| US20100137313A1 (en) * | 2008-10-03 | 2010-06-03 | Astrazeneca Ab | Heterocyclic derivatives and methods of use thereof |
| CA2815330A1 (en) | 2010-11-09 | 2012-05-18 | Cellzome Limited | Pyridine compounds and aza analogues thereof as tyk2 inhibitors |
| EP2763976B1 (en) | 2011-10-05 | 2016-05-18 | Merck Sharp & Dohme Corp. | 2-pyridyl carboxamide-containing spleen tyrosine kinase (syk) inhibitors |
| EP2840080B1 (en) | 2012-04-17 | 2017-12-06 | FUJIFILM Corporation | Nitrogen-containing heterocyclic compound or salt thereof |
| AU2018243691B2 (en) * | 2017-03-27 | 2022-05-12 | Cardurion Pharmaceuticals, Llc | Heterocyclic compound |
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2020
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| WO2002011724A2 (en) | 2000-08-08 | 2002-02-14 | Ortho-Mcneil Pharmaceutical, Inc. | Neuroprotective 2-pyridinamine compositions and related methods |
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| US20200230137A1 (en) | 2020-07-23 |
| TW201904959A (zh) | 2019-02-01 |
| TWI789381B (zh) | 2023-01-11 |
| KR20200027917A (ko) | 2020-03-13 |
| CA3058182A1 (en) | 2018-10-04 |
| US11197858B2 (en) | 2021-12-14 |
| EP3600327A4 (en) | 2020-10-28 |
| CN110799190B (zh) | 2024-04-19 |
| CN110799190A (zh) | 2020-02-14 |
| US10543212B2 (en) | 2020-01-28 |
| JP7249950B2 (ja) | 2023-03-31 |
| WO2018183112A1 (en) | 2018-10-04 |
| US20180280389A1 (en) | 2018-10-04 |
| JP2020515575A (ja) | 2020-05-28 |
| AU2018243691B2 (en) | 2022-05-12 |
| EP3600327A1 (en) | 2020-02-05 |
| AU2018243691A1 (en) | 2019-10-24 |
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